iSCORE: Immunotherapy Sequencing in COlon and REctal Cancer

This is a single-arm, single centre open-label, phase II interventional clinical trial of combination immunotherapy with Nivolumab and Relatlimab in mCRC. Patients with metastatic RAS/RAF WT colorectal cancer who have previously had a radiological response to EGFR inhibitors i.e. Cetuximab or Panitumumab, either combined with chemotherapy or as single agents, but subsequently experienced progression of their disease will be eligible for the study. They will consent to the study ideally within 3 months having progressed/ become refractory to EGFR blockable and undergo a mandatory baseline biopsy within this time period. Patients will receive Nivolumab and Relatlimab every 4 weeks and will start on study treatment as soon as possible after the baseline biopsy. After starting on the study drugs, there will be a mandatory 'on-treatment' biopsy at day 21 ± 3 days. Response assessments in the form of either CT or MRI scans will take place every 8 weeks throughout the study for the 12 months and every 12 weeks from 12 months onwards. Patients will continue on the study until progressive disease (PD) is confirmed by RECIST 1.1 or when maximum duration of treatment of 24 months has been reached There will be the possibility of 'treating beyond progression' if participants are deriving clinical benefit from treatment to encompass the possibility of pseudoprogression. At PD participants will undergo a further biopsy. The investigators envisage enrolling a total of 25 participants and the investigators anticipate 30 months as a feasible time frame for accrual.